Dataset Information

Reproducibility of nasal allergen challenge responses in adults with allergic rhinitis.

ABSTRACT: Background:Allergic rhinitis is characterized by nasal inflammation in response to allergen exposure. Nasal allergen challenges are used in clinical trials evaluating drug effects. Reproducibility of nasal secretion cytokine responses and physiological measurements are needed to determine the optimum measurements and power calculations for future studies. We have investigated the reproducibility of nasal cytokine measurements, using ready-to-use polyvinyl acetate sponges to collect nasal secretions, and measurements of nasal physiological responses. Methods:Twelve subjects with allergic rhinitis and no history of respiratory disease, and 12 subjects with asthma and allergic rhinitis underwent a nasal allergen challenge. This was repeated at 7-14 days later. Results:There were increases in IL-5, CCL11, and CXCL8 responses post-challenge (all P<0.05). There was better reproducibility at later time points when higher cytokine levels were detected for IL-5 (ri =0.64 at 8 hours) and CXCL8 (ri =0.91 at 8 hours). Acoustic rhinometry provided good to excellent reproducibility (ri =0.66-0.89). Rhinomanometry had lower reproducibility with greater variation (ri =0.10-0.70), with some subjects unable to perform the measurement. Multiplex immunoassays provided greater sensitivity for CCL11 measurements. There were no differences between allergic rhinitis patients with and without asthma. Conclusion:Polyvinyl acetate sponges are a practical and reproducible way to sample nasal secretions. Acoustic rhinometry is a practical and reproducible method for assessing physiological responses. There were no differences in nasal response due to the presence of concurrent asthma.

SUBMITTER: Pantin CT

PROVIDER: S-EPMC6521845 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Reproducibility of nasal allergen challenge responses in adults with allergic rhinitis.

Pantin Charles T CT Southworth Thomas T Wetzel Kristiane K Singh Dave D

Clinical pharmacology : advances and applications 20190513

<h4>Background</h4>Allergic rhinitis is characterized by nasal inflammation in response to allergen exposure. Nasal allergen challenges are used in clinical trials evaluating drug effects. Reproducibility of nasal secretion cytokine responses and physiological measurements are needed to determine the optimum measurements and power calculations for future studies. We have investigated the reproducibility of nasal cytokine measurements, using ready-to-use polyvinyl acetate sponges to collect nasal ...[more]

PMID: 31191044

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Project description:Background:The Allergic Rhinitis Clinical Investigator Collaborative (AR-CIC) is a network of experienced Allergic Rhinitis (AR) researchers developing better research tools based on the nasal allergen challenge (NAC). A key objective of such is the ability to detect efficacy in a small population. AR-CIC sought to test its NAC protocol as a secondary objective in two small mechanistic research trials of a novel form of immunotherapy [Cat Peptide Antigen Desensitisation (Cat-PAD)] for which efficacy had previously been demonstrated. The primary objective (not presented here) was to identify potential biomarkers of efficacy for peptide immunotherapy, and this provided an ideal opportunity to corroborate the NAC protocol. We aim to clinically validate the AR-CIC NAC methodology in a pooled analysis of secondary endpoints measured in two open label mechanistic studies of cat allergic participants treated with Cat-PAD. Methods:Cat allergic AR sufferers with ongoing cat exposure were included. Participants had to demonstrate a total nasal symptom score (TNSS) of at least 8 (max 12) and/or achieve a reduction in peak nasal inspiratory flow (PNIF) of ??50% during a screening titrated NAC. Eligible participants then underwent a baseline NAC visit with the allergen dose that produced a positive challenge at screening, followed by four monthly injections of 6 nmol Cat-PAD. A follow up NAC visit documented changes in nasal response 1 month following the completion of treatment. Results:Nineteen subjects completed the study protocol in the two studies combined. Four injections of Cat-PAD resulted in a significant reduction in TNSS responses generated via NAC following allergen challenge (15 min p?<?0.05, 30 min p?<?0.05, 1 h p?<?0.01, 2 h p?<?0.05). There was modest correlation between symptom scores and PNIF measurements. Conclusions:This study supports the validity of the AR-CIC's optimised NAC protocol for conducting research of the potential efficacy of novel therapeutics in multi-centre studies.Trial registration Both studies reported herein were registered clinicaltrials.gov (NCT01383590 and NCT01383603).

Project description:ObjectiveTo determine effects of probiotic consumption on clinical and immunological parameters of seasonal allergic rhinitis (SAR) in an out-of-season single nasal allergen challenge.MethodsIn a study registered at ClinicalTrials.Gov (NCT01123252), a 16-week dietary intervention was undertaken in 60 patients with allergic rhinitis (>16 years old). Using a double-blinded, placebo-controlled anonymised design, the patients were divided equally into two groups. One group was given a dairy drink containing Lactobacillus casei Shirota to ingest daily while the other consumed a similar drink without bacteria. Participants attended the clinic on two consecutive days before the intervention and then again at the end of the study period. On the first day of each 2-day visit, following clinical examination, assessments were made of total nasal symptoms scores and peak nasal inspiratory flow. Nasal scrapings, nasal lavage and blood were collected for laboratory analyses of cellular phenotypes, soluble mediator release and in vitro responses to pollen allergen. These procedures were repeated 24 hours following nasal allergen challenge.ResultsPrior to and following intervention there were no detectable differences between study groups in measured clinical outcome. After intervention, there were differences between groups in their percentages of CD86+ epithelial cells (p = 0.0148), CD86+CD252+ non-epithelial cells (p = 0.0347), sIL-1RII release (p = 0.0289) and IL-1β (p = 0.0224) levels at the nasal mucosa. Delivery of probiotic also suppressed production of sCD23 (p = 0.0081), TGF-β (p = 0.0283) and induced increased production of IFN-γ (p = 0.0351) in supernatants of cultured peripheral blood.Conclusions & clinical relevanceThis study did not show significant probiotic-associated changes with respect to the primary clinical endpoint. An absence of overt clinical benefit may be due to an inability of single nasal challenges to accurately represent natural allergen exposure. Nevertheless, oral delivery of probiotics produced changes of the immunological microenvironment at the nasal mucosa in individuals affected by SAR.Trial registrationClinicalTrials.Gov NCT01123252.

Project description:BackgroundNasal provocation testing (NPT) is a reference methodology to identify the culprit allergen in patients with allergic rhinitis. Selecting the right allergen for NPT is particularly difficult in poly-sensitized patients with seasonal allergic rhinitis (SAR). Predictors of NPT outcomes may facilitate the proper use of this test or even substitute it.ObjectiveTo identify predictors of grass pollen NPT outcome from an array of clinical data, e-diary outcomes, and allergy test results in poly-sensitized pediatric patients with SAR.MethodsPoly-sensitized, SAR patients with grass pollen allergy, participating in the @IT.2020 pilot project in Rome and Pordenone (Italy), participated in a baseline (T0) visit with questionnaires, skin prick testing (SPT), and blood sampling to measure total (ImmunoCAP, TFS, Sweden) and specific IgE antibodies to grass pollen extracts and their major allergenic molecules (ESEP, Euroimmun Labordiagnostika, Germany). During the pollen season, patients filled the AllergyMonitor® e-diary app measuring their symptoms, medication intake, and allergy-related well-being via the Visual Analogue Scale (VAS). After the pollen season (T1), patients answered clinical questionnaires and underwent a nasal provocation test (NPT) with grass pollen extract.ResultsWe recruited 72 patients (age 14.3 ± 2.8 years, 46 males) sensitized to grass and/or other pollens, including olive (63; 87.5%) and pellitory (49; 68.1%). Patients positive to grass pollen NPT (61; 84.7%), compared to the negative ones, had worse VAS values in the e-diary, larger SPT wheal reactions, and higher IgE levels, as well as specific activity to timothy and Bermuda grass extracts, rPhl p 5 and nCyn d 1. A positive NPT to grass pollen was predicted by an index combining the specific activity of IgE towards Phl p 5 and Cyn d 1 (AUC: 0.82; p < 0.01; best cut-off ≥7.25%, sensitivity 70.5%, specificity: 90.9%). VAS results also predicted NPT positivity, although with less precision (AUC: 0.77, p < 0.01; best cut-off ≥7, sensitivity: 60.7%, specificity: 81.8%).ConclusionsAn index combining the specific activity of IgE to rPhl p 5 and nCyn d 1 predicted with moderate sensitivity and high specificity the outcome of a grass pollen NPT in complex, poly-sensitized pediatric patients with seasonal allergic rhinitis. Further studies are needed to improve the index sensitivity and to assess its usefulness for NPT allergen selection or as an alternative to this demanding test procedure.

Project description:IntroductionAlthough recent studies have shown that the human microbiome is involved in the pathogenesis of allergic diseases, the impact of microbiota on allergic rhinitis (AR) and non-allergic rhinitis (nAR) has not been elucidated. The aim of this study was to investigate the differences in the composition of the nasal flora in patients with AR and nAR and their role in the pathogenesis.MethodFrom February to September 2022, 35 AR patients and 35 nAR patients admitted to Harbin Medical University's Second Affiliated Hospital, as well as 20 healthy subjects who underwent physical examination during the same period, were subjected to 16SrDNA and metagenomic sequencing of nasal flora.ResultsThe microbiota composition of the three groups of study subjects differs significantly. The relative abundance of Vibrio vulnificus and Acinetobacter baumanni in the nasal cavity of AR patients was significantly higher when compared to nAR patients, while the relative abundance of Lactobacillus murinus, Lactobacillus iners, Proteobacteria, Pseudomonadales, and Escherichia coli was lower. In addition, Lactobacillus murinus and Lacttobacillus kunkeei were also negatively correlated with IgE, while Lacttobacillus kunkeei was positively correlated with age. The relative distribution of Faecalibacterium was higher in moderate than in severe AR patients. According to KEGG functional enrichment annotation, ICMT(protein-S-isoprenylcysteine O-methyltransferase,ICMT) is an AR microbiota-specific enzyme that plays a role, while glycan biosynthesis and metabolism are more active in AR microbiota. For AR, the model containing Parabacteroides goldstemii, Sutterella-SP-6FBBBBH3, Pseudoalteromonas luteoviolacea, Lachnospiraceae bacterium-615, and Bacteroides coprocola had the highest the area under the curve (AUC), which was 0.9733(95%CI:0.926-1.000) in the constructed random forest prediction model. The largest AUC for nAR is 0.984(95%CI:0.949-1.000) for the model containing Pseudomonas-SP-LTJR-52, Lachnospiraceae bacterium-615, Prevotella corporis, Anaerococcus vaginalis, and Roseburia inulinivorans.ConclusionIn conclusion, patients with AR and nAR had significantly different microbiota profiles compared to healthy controls. The results suggest that the nasal microbiota may play a key role in the pathogenesis and symptoms of AR and nAR, providing us with new ideas for the treatment of AR and nAR.

Dataset Information

Reproducibility of nasal allergen challenge responses in adults with allergic rhinitis.

Publications

Reproducibility of nasal allergen challenge responses in adults with allergic rhinitis.

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